Coordination of Cell Division and Differentiation 383
inhibits cell division in leaves, which contain less but larger cells (Wang et al.
2000; De Veylder et al. 2001). This effect is partially reversed by overexpres-
sion ofCYCD3(Zhou et al. 2003), an inducer of cell division. Similarly, the
altered leaf phenotype of plants expressingCYCD3ectopically is reversed by
overexpression of tobacco CDK inhibitor (KIS1) (Jasinski et al. 2002). In-
terestingly,KRP1overexpression does not have an appreciable effect on cell
fate specification that occurs independently of changes in endoreplication
level (Weinl et al. 2005). The function of KRP2 seems to be exerted through
CDKA;1 and, when overexpressed in mitotically dividing cells, it also has
an effect on endocycle progression (Verkest et al. 2005). Maize KRP1 and
KRP2 play a role in endocycle control through inhibition of the endosperm-
associated CDK activity, and consequently during maize endosperm forma-
tion (Coelho et al. 2005).
CDK activity, modulated by specific cyclins and CDK inhibitors, seems to
be one of the limiting components, most likely not the only one, that regulate
the arrested state of pericycle cells before triggering the lateral root initiation
program (Casimiro et al. 2003; Vanneste et al. 2005). Pericycle cells contain
high levels ofCDKAandKRP2transcripts, but lackCYCB1(Himanen et al.
2002), likely contributing to maintenance of cell cycle arrest. Pericycle cells
can be synchronized by treatment with the auxin transport inhibitor NPA
and the released again upon auxin application (Himanen et al. 2002). With
this system, over 900 genes have been identified to change specifically dur-
ing lateral root initiation (Himanen et al. 2004). Thus, auxin addition triggers
the expression ofCYCD3;1,E2Faandhistone H4genes, which are quickly in-
duced, thenCDKBwas induced, although later than the S-phase genes. In
addition, the expression of CDK inhibitorsKRP1andKRP2was rapidly and
strongly reduced (Himanen et al. 2002).
2.2
Retinoblastoma, E2F-DP Transcription Factors and their Targets
CDK activity drives cell cycle transitions by phosphorylating specific tar-
gets. Changes in their phosphorylation state allows the transition from G1 to
S, through S and from G2 to M. In G1/S, the retinoblastoma-related (RBR)
protein is the main target of G1 CDKs (Nakagami et al. 1999; Boniotti and
Gutierrez 2001; Nakagami et al. 2002). RBR is a negative regulator of cell pro-
liferation, as revealed by loss-of-function mutations in theRBRgene, which
results in an impairment to restricts mitosis in the haploid nuclei of the
female gametophyte (Ebel et al. 2004). Local inactivation ofRBRinArabidop-
sisroots stimulates stem cell renewal, as it occurs in plants overexpressing
CYCD3;1orE2Fa-DPa(Wildwater et al. 2005).
One of the major roles of RBR is to repress the expression of genes regu-
lated by the E2F/DP family of transcription factors, as discussed below. Recent
evidence derived from RBR protein inactivation strategies is consistent with